TY - JOUR
T1 - Arachidonic Acid Metabolites Mediate Angiotensin II-Induced NADH/NADPH Oxidase Activity and Hypertrophy in Vascular Smooth Muscle Cells
AU - Zafari, A. Maziar
AU - Ushio-Fukai, Masuko
AU - Minieri, Candace A.
AU - Akers, Marjorie
AU - Lassègue, Bernard
AU - Griendling, Kathy K.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - Previously, we showed that angiotensin II stimulation of the NADH/NADPH oxidase is involved in hypertrophy of cultured vascular smooth muscle cells (VSMC). Here, we examine the pathways leading to oxidase activation, and demonstrate that arachidonic acid metabolites mediate hypertrophy by activating the p22phox-based NADH/NADPH oxidase. Angiotensin II stimulates phospholipase A2, releasing arachidonic acid, which stimulates oxidase activity in vitro. When arachidonic acid metabolism is blocked with 5,8,11,14- eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA), oxidase activity decreases by 80 ± 10%. In VSMC transfected with antisense p22phox to attenuate NADH/NADPH oxidase expression, arachidonic acid is unable to stimulate NADH/NADPH-dependent superoxide production. In these cells, or in cells in which NADH/NADPH oxidase activity is inhibited by diphenylene iodonium, angiotensin II-induced [3H]leucine incorporation is also inhibited. Attenuation of oxidase activation by inhibiting arachidonic acid metabolism with ETYA, NDGA, baicalein, or SKF-525A also inhibits angiotensin II-stimulated protein synthesis (74 ± 2% and 34 ± 1%, respectively). Thus, endogenous noncyclooxygenase arachidonic acid metabolites mediate angiotensin II-stimulated protein synthesis in cultured VSMC by activating the NADH/NADPH oxidase, providing mechanistic evidence for redox control of VSMC hypertrophy.
AB - Previously, we showed that angiotensin II stimulation of the NADH/NADPH oxidase is involved in hypertrophy of cultured vascular smooth muscle cells (VSMC). Here, we examine the pathways leading to oxidase activation, and demonstrate that arachidonic acid metabolites mediate hypertrophy by activating the p22phox-based NADH/NADPH oxidase. Angiotensin II stimulates phospholipase A2, releasing arachidonic acid, which stimulates oxidase activity in vitro. When arachidonic acid metabolism is blocked with 5,8,11,14- eicosatetraynoic acid (ETYA) or nordihydroguaiaretic acid (NDGA), oxidase activity decreases by 80 ± 10%. In VSMC transfected with antisense p22phox to attenuate NADH/NADPH oxidase expression, arachidonic acid is unable to stimulate NADH/NADPH-dependent superoxide production. In these cells, or in cells in which NADH/NADPH oxidase activity is inhibited by diphenylene iodonium, angiotensin II-induced [3H]leucine incorporation is also inhibited. Attenuation of oxidase activation by inhibiting arachidonic acid metabolism with ETYA, NDGA, baicalein, or SKF-525A also inhibits angiotensin II-stimulated protein synthesis (74 ± 2% and 34 ± 1%, respectively). Thus, endogenous noncyclooxygenase arachidonic acid metabolites mediate angiotensin II-stimulated protein synthesis in cultured VSMC by activating the NADH/NADPH oxidase, providing mechanistic evidence for redox control of VSMC hypertrophy.
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U2 - 10.1089/ars.1999.1.2-167
DO - 10.1089/ars.1999.1.2-167
M3 - Article
C2 - 11228745
AN - SCOPUS:0033140218
SN - 1523-0864
VL - 1
SP - 167
EP - 179
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 2
ER -